Chronically elevated blood levels of cholesterol lead to cardiovascular disease as the cholesterol finds its way into the walls of blood vessels and damages them. This ultimately results in symptoms of chronic arterial insufficiency such as angina and claudication on the one hand, and acute vascular insufficiency, such as heart attack and stroke on the other.
Over $120 billion dollars is spent on direct and indirect costs associated with cardiovascular disease annually in the United States alone. Cardiovascular disease incidence increases with serum LDL cholesterol in a log linear fashion and more importantly declines with treatment-induced reduction of serum LDL cholesterol.
Conventional therapy for elevated blood cholesterol levels takes the form of four classes of FDA approved medications: statins, bioresins, fibrates, and niacin.
Of these, statins are the most widely used with greater than $20 billion in annual sales; however, all the classes, including statins, have side effects and at higher doses, that are necessary to achieve targets, result in side effects that limit their utility. This is especially so of niacin and statins.
Recently, it has been appreciated that in attempting to lower cholesterol, two or more drugs with different mechanisms of action can lower toxicity and produce synergy in the cholesterol lowering effect. Vytorin, a recently introduced combination of Zetia and Simvastatin, has been shown to decrease cholesterol absorption and synthesis and reduce cholesterol better than the sum of the expected reduction of either drug alone. This is explained by a phenomenon I refer to as “escape homeostasis.” When one pathway to cholesterol elevation is blocked, an alternative pathway is often enhanced by the body, so that the overall cholesterol levels are maintained. There is, thus, a built-in or automatic drug resistance that can only be overcome with multiple active agents working simultaneous at different sites. It is noteworthy that evidence exists that even homeopathic, previously felt sub-therapeutic amounts of biologically active cholesterol lowering compounds can exert powerful efficacy with minimal side effects when combined with other agents that work by alternative pathways.